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Current Molecular Pharmacology

Shivani Verma, Saurabh Sharma
Protein tyrosine phosphatase (PTP) class of enzymes functions in a unit with protein tyrosine kinases to regulate signaling pathways. Several members of the PTP family link to human disease predisposition such as PTP1B, SH2, DEP1, and inhibition of these enzymes may represent an effective palliative therapy. Protein tyrosine phosphatase inhibition has been intensively investigated as an important therapeutic target against metabolic syndrome and has been documented to improve hepatic insulin sensitivity, reduce liver triglycerides, cholesterol levels, and protects against endoplasmic reticulum (ER) stress...
February 26, 2018: Current Molecular Pharmacology
Mohsen Cheki, Rasoul Yahyapour, Bagher Farhood, Abolhassan Rezaeyan, Dheyauldeen Shabeeb, Peyman Amini, Saeed Rezapoor, Masoud Najafi
BACKGROUND: Each year, millions of people die from cancer. Radiotherapy is one of the main treatment strategies for cancer patients. Despite the beneficial roles of treatment with radiation, several side effects may threaten normal tissues of patients in the years after treatment. Moreover, high incidences of second primary cancers may reduce therapeutic ratio of radiotherapy. The search for appropriate targets of radiosensitization of tumor cells as well as radioprotection of normal tissues is one of the most interesting aims in radiobiology...
February 18, 2018: Current Molecular Pharmacology
Nabeela Khadija Dulull, Daniel Anthony Dias, Thilini Rasika Thrimawithana, Faith Ai Ai Kwa
BACKGROUND: In age-related macular degeneration, oxidative damage and abnormal neovascularization in the retina are caused by the upregulation of vascular endothelium growth factor and reduced expression of Glutathione-S-transferase genes. Current treatments are only palliative. Compounds from cruciferous vegetables (e.g. L-Sulforaphane) have been found to restore normal gene expression levels in diseases including cancer via the activity of histone deacetylases and DNA methyltransferases, thus retarding disease progression...
January 25, 2018: Current Molecular Pharmacology
Jessica Felton, Shien Hu, Jean-Pierre Raufman
BACKGROUND: Expression and activation of subtype-3 muscarinic receptors (M3R) plays an important role in the progression of colorectal neoplasia. METHODS: Herein, we describe the role of muscarinic receptors in colon cancer, focusing specifically on M3R, illustrate how M3R over-expression and activation of post-receptor signaling pathways potentiates tumor progression, and explore the efficacy and safety of a variety of therapeutic approaches that can target the molecules involved...
January 18, 2018: Current Molecular Pharmacology
George Liapakis
No abstract text is available yet for this article.
2018: Current Molecular Pharmacology
Michael Kahn
No abstract text is available yet for this article.
2018: Current Molecular Pharmacology
Rasoul Yahyapour, Peyman Amini, Saeed Rezapoor, Abolhasan Rezaeyan, Bagher Farhood, Mohsen Cheki, Hengameh Fallah, Masoud Najafi
Inflammation is the response of the immune system that guards the body against several harmful stimuli in normal conditions. However, in response to ionizing radiation that leads to a massive cell death and DNA aberrations, this phenomenon causes various side effects in normal tissues. Inflammation is involved in various side effects such as gastrointestinal toxicity, mucositis, skin reactions, nervous system damage, pneumonitis, fibrosis and so on. Observations have proposed that inflammatory mediators are involved in the toxic effect of ionizing radiation on non-irradiated cells via a phenomenon named bystander effect...
November 8, 2017: Current Molecular Pharmacology
Maria Letizia Motti, Stefania D'Angelo, Rosaria Meccariello
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs able to regulate gene expression at multiple levels. They are detected in tissues, blood, and other body fluids with high stability and have a recognized role in the maintaining of tissue homeostasis. Aberrant expression profile of miRNAs has been observed in several diseases, primarily cancer. As a consequence, the analysis of miRNA signature has recognized diagnostic and prognostic role in human diseases, and the development of miRNA-based therapies is currently under investigation...
October 13, 2017: Current Molecular Pharmacology
Pricila Pflüger, Gabriela Gregory Regner, Vanessa R Coelho, Lucas Lima da Silva, Leopoldo Nascimento, Cassiana Macagnan Viau, Régis Adriel Zanette, Cleonice Hoffmann, Jaqueline Nascimento Picada, Jenifer Saffi, Patrícia Pereira
Gamma-decanolactone (GD) is a monoterpene effective against seizures induced by pentylenetetrazole. The mechanism of action of GD is likely to be via glutamate antagonism. GD also inhibits intracellular reactive oxygen species (ROS) generation and the lipopolysaccharide-induced expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) in vitro. Considering the neuropharmacological profile of GD studied so far, we investigated the effect of intraperitoneal administration of GD 100 and 300 mg/kg on pilocarpine (PIL)-induced status epilepticus (SE) in mice...
October 2, 2017: Current Molecular Pharmacology
Yi Zhao, Kaijin Wu, Yongfeng Wu, Elizabeth Melendez, Goar Smbatyan, David Massiello, Michael Kahn
The development of the tyrosine kinase inhibitor Imatinib (IM) represents a milestone breakthrough in CML (Chronic Myeloid Leukemia) treatment. However, it is not curative and patients develop IM resistance. IM resistance has been previously correlated with the emergence of drug-resistant LIC/LSC (Leukemia Initiating Cell/Leukemia Stem Cell) and increased nuclear catenin levels and enhanced Wnt signaling. It has been demonstrated previously that drug resistant CML LIC/LSC can be safely eliminated both in vitro and in vivo via disruption of the CBP/catenin interaction, utilizing the highly biochemically selective small molecule CBP/catenin antagonist ICG-001...
September 19, 2017: Current Molecular Pharmacology
Gangadhar Matharasala, Ganesh Samala, Yogeeswari Perumal
The objective of present study is to explore multiple effects of the compound MG17 and relate them to achieve better therapeutic potential against neuroinflammation related disorders. We examined whether our compound is acting through regulating neuroinflammatory mediators. We have done some preliminary behavioral studies to shortlist the derivatives using rodent models of peripheral nerve injury in our earlier publication and now we extended our screening studies to explore the test compounds efficacy on other related peripheral neurological disorders such as Streptozotocin-induced diabetic peripheral neuropathy (DPN) and methyl mercury (MeHg) induced neurodegeneration in rats...
September 19, 2017: Current Molecular Pharmacology
Hamidreza Famitafreshi, Morteza Karimian
INTRODUCTION: Addiction is a compulsive drug-seeking and drug-taking behavior. Reduction of high-risk behaviors can reduce the burden of addiction in society and can improve the overall prognosis of drug addiction. The aim of this study is to show that reduction of oxidative stress with socialization will reduce occurrence of high-risk behavior during addiction period. METHODS AND MATERIALS: Fifty-four male Sprague-Dawley rats were randomly divided into four groups: socialized, isolated, addicted socialized and addicted isolated...
September 19, 2017: Current Molecular Pharmacology
Abeer M Rababa'h, Tamara B Hijjawi, Karem H Alzoubi, Saddam Al Demour, Mera A Ababneh
Imipenem has played an important role in the treatment of broad-spectrum bacterial infection. However, nephrotoxicity due to imipenem remains an important clinical challenge. The aim of this study is to test the hypothesis stating that N-acetyl-L-cysteine (NAC) and atorvastatin possess a nephroprotective effect against imipenem-induced nephrotoxicity. Adult Sprague Dawley rats were randomly assigned into six groups (n=8-10 rats/group; total n=55). The groups were (control, imipenem only, NAC only, atorvastatin only, NAC with imipenem, and atorvastatin with imipenem)...
July 31, 2017: Current Molecular Pharmacology
Ludovic Ventura, Félix Carvalho, Ricardo Jorge Dinis-Oliveira
New psychoactive substances (NPS), often referred to as "legal highs" or "designer drugs", are derivatives and analogues of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. Due to inefficient monitoring techniques, as well as limited knowledge concerning long-time effects of NPS, further studies regarding such compounds are constantly required. This systematic review aims to gather the state of the art regarding chemical, molecular pharmacology and toxicological information of opioid class of NPS...
July 4, 2017: Current Molecular Pharmacology
Daryoush Hamidi Alamdari, Malihe Aghasizadeh-Sharbaf, Maryam Mohadjerani, Gordon A Ferns, Amir Avan
BACKGROUND: Diabetes mellitus (DM) is a major health problem with an increasing global prevalence. It is usually associated with an imbalance between pro-oxidant mechanisms and antioxidant defenses, contributing to oxidative-stress, and this leads to an increased susceptibility to endothelial dysfunction, atherosclerosis, insulin-resistance and impaired-pancreatic β-cell function. OBJECTIVE: We have assessed the Prooxidant-antioxidant balance (PAB) and anti-haemolytic effect of Thuja orientalis L using the PAB assay and the analysis of hematological markers...
April 4, 2017: Current Molecular Pharmacology
Nina Dedic, Alon Chen, Jan M Deussing
Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and consequently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2...
March 1, 2017: Current Molecular Pharmacology
Yvette Taché, Muriel Larauche, Pu-Qing Yuan, Mulugeta Million
Corticotropin-releasing factor (CRF) signaling pathways coordinate the behavioral, endocrine, autonomic and visceral responses to stress. Convergent anatomical, molecular, pharmacological and functional experimental evidence supports an important role of brain CRF receptor signaling in stress-related alterations of gastrointestinal functions. These include the inhibition of gastric acid secretion and gastro-small intestinal transit, the stimulation of colonic enteric nervous system and secretory-motor function, enhanced intestinal permeability, and visceral hypersensitivity...
February 23, 2017: Current Molecular Pharmacology
Antonis Makrigiannakis, Thomas Vrekoussis, Emmanouel Zoumakis, Iordanis Navrozoglou, Sophia Kalantaridou
Corticotropin releasing hormone (CRH), the main peptide-mediator of stress, has been found in the female reproductive system. Herein, the role of CRH receptors in the female reproductive sysem is presented. It is clear that CRH receptors are involved in the regulation of the hypothalamic-pituitary-ovarian axis, while locally are associated with decidualization, embryonic implantation, early fetal development and triggering of parturition. Abnormal CRH signalling may contribute to obstetrical pathophysiology, such as pre-eclampsia, abnormal placenta invasion, endometrial growth retardation and preterm delivery...
February 23, 2017: Current Molecular Pharmacology
Craig Basman, Pratik Agrawal, Richard Knight, Louis Saravolatz, Chad McRee, Carol Chen-Scarabelli, Jagat Narula, Tiziano Scarabelli
There has been a constant pursuit for development of newer therapies which can contribute to the relatively nascent field of cardioprotection in the setting of myocardial ischemia-reperfusion injury. One novel cardioprotective agent among others, that has shown promising results in the limited number of research studies undertaken till now, is Urocortin. Urocortins are peptides belonging to the Corticotropin-Releasing Hormone family. Acting through a variety of downstream mechanisms, urocortin has been shown to alter cellular metabolism and modulate the mechanism of cell death occurring as a result of ischemia-reperfusion injury...
February 22, 2017: Current Molecular Pharmacology
Arnau Cordomi, George Liapakis, Minos Timotheos Matsoukas
The corticotropin-releasing factor type 1 and 2 receptors (CRF1R and CRF2R) belong to the secretin-like family, also known as class B1, of G protein-coupled receptors (GPCRs). Several endogenous hormones mediate their responses through the CRF receptors, such as CRF and the urocortins. The structures for the N-terminus extracellular domain of both CRF1R and CRF2R in complex with peptidic ligands were released a few years ago and permitted the study of hormone binding to the orthosteric binding site. It was not until more recently, when the crystal structure of the transmembrane domain of human CRF1R in its inactive state bound to an allosteric antagonist became available...
January 10, 2017: Current Molecular Pharmacology
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